As disclosed in copending U.S. Patent application Ser. No. 07/320,484, in the names of Larner, Kennington, Huang and Shen, successful purification, to essential homogeneity, of at least two substances appearing to mediate the activity of insulin, particularly in terms of activation of pyruvate dehydrogenase, as well as the inhibition of other enzyme systems, has been achieved. Structural analysis of the insulin mediator possessing the biological activity of activating pyruvate dehydrogenase (PDH) has surprisingly identified this mediator to be comprised of a glycophosphatidylinositol anchor-type molecule comprising the optically active carbohydrate D-chiro-inositol. Further research as disclosed in U.S. Patent application Ser. No. 07/476,953, inventors Larner, Kennington and Shen, have demonstrated that D-chiro-inositol is either absent, or present in extremely low levels, in type II, insulin-resistant diabetics, in contrast to the levels observed in non-diabetic control individuals As an example, the average concentration of D-chiro-inositol in control non-diabetic individuals is about 900 nanograms per milliliter. The level in type II diabetics is uniformly below about 200 nanograms. On the basis of this distinction, a screening diagnostic has been established, to determine the presence or absence of D-chiro-inositol in the urine and other body fluids. An absence of D-chiro-inositol is evidence of a genetic predisposition for the development of clinical symptoms of type II diabetes, or confirmation of the presence of type II diabetes in those exhibiting some or all of the classical, clinical symptoms.
Further research has indicated that insulin-resistant diabetes may in fact be due to a genetic inability to synthesize, in vivo, D-chiro-inositol, an essential carbohydrate of the insulin mediator responsible for activation of PDH. This chiro sugar is not available in sufficient quantities in conventional diets to compensate for the deficiency in the synthetic pathway necessary to synthesize this compound, and thereby build the insulin mediator. In the absence of the insulin mediator, administration of insulin will not address the symptoms of type II diabetes.
Accordingly, it remains an object of those skilled in the art to find an effective treatment to prevent the development of clinical, symptomatic type II insulin-resistant diabetes in those genetically predisposed to that development, and to intervene in those exhibiting clinical symptoms of type II diabetes.